Mammalian cells in vitro will be studied in order to complete the definition of radiation killing, heat killing, and heat radiosensitization during the mammalian cell cycle, with emphasis on treating cells at the G1-S transition or in G2. Effects of lowering the pH and treating cells with membrane active agents and with agents that reduce concentrations of intracellular ATP will be studied. Endpoints will include cell killing, mutation induction, and chromosomal aberrations, as well as time of death or lysis as monitored by time lapse cinematography. Emphasis will be placed on studying the effects of low pH and nutrient deprivation on the indiction of thermotolerance and how the development and loss of thermotolerance is affected by cell cycle progression of viable cells. Also, the influence of low pH and nutrient deprivation of the effect of varying the sequence between heat and radiation will be studied. Finally, heat sensitive and heat resistant mutants, including hybrids of the two, will be obtained in order to relate heat killing with heat radiosensitization during the mammalian cell cycle.